It has been proposed that the high incidence of obesity in the Pima Indians may be due to genetic selection for a "thrifty gene", a gene that would predispose the Pimas to store energy very efficiently. In order to determine whether or not such a genetic difference exists, resting metabolic rates and responses to three thermogenic stimuli (food, norepinephrine-infusions, and exercise) were measured during a period of weight maintenance and after 3 weeks of overfeeding. The studies in overweight subjects had been completed last year. We now studied some lean Pimas in order to find out, whether the observations made in overweight subjects are common in all members of this tribe or rather a result of the obesity. The major finding so far is, that obese Pimas, although having similar basal plasma concentrations of norepinephrine to Caucasians, achieve much higher blood levels of the hormone during identical norepinephrine-infusions. These results strongly suggest that obese Pimas have a clearance defect for norepinephrine. Turnover studies will have to confirm these data. Plasma norepinephrine analyses are in progress at this time. Their results will enable us to compare the very interesting findings in the overweight Pimas with that of normal weight subjects of the same tribe. Furthermore, related to this probable disorder of the sympathetic nervous system, we found that the thermogenic response to norepinephrine was blunted after overfeeding in both the lean and obese Pimas, while no such changes could be observed in previous studies in Caucasians. Future plans for thermogenesis include thyroid kinetic studies on lean Pimas and norepinephrine kinetics on both lean and obese Pimas.